The pursuit of international collaborative research efforts will lead to effective strategies which lower oral cancer incidence and mortality. We present a two year planning proposal based on a multi-institutional collaboration consisting of the Strang Cancer Prevention Center, New York Medical College, and American Health Foundation in New York City, the AC Camargo Cancer Center/Ludwig Institute for Research in Sao Paulo, Brazil, the Free University Hospital in Amsterdam, the Netherlands, the National Cancer Center of Singapore, and the Tata Memorial Center in Bombay. These combined centers evaluate over 3000 oral cancer patients annually. Combined with an experienced team of scientists with expertise in epidemiology, carcinogenesis, tumor and molecular biology, and clinical trials, this collaborative team is well-equipped to address critical questions in oral oncology. Specifically, we propose to: 1) Develop a case-control international epidemiologic trial to investigate factors responsible for changing trends in oral cancer incidence; specifically, an increased incidence of oral cancer in the young adult; 2) Add measures of genetic susceptibility to the case- control study in order to enhance risk factor estimates. Genetic susceptibility markers will likewise be evaluated as a contributing factor to disease in the young adult population; 3) Determine the impact of levels of environmental exposures including the various forms of tobacco and alcohol identified in the case-control study on the pattern of genetic mutations within oral cancers. The optimal molecular measures and standardization of molecular assays will be established during this planning period; and 4) Develop a chemopreventive strategy in high risk populations for oral cancer. The proposed planning period will provide for project development. It will establish feasibility of conducting subsequent detailed protocols. Plans for additional centers will be implemented as necessary in order to meet objectives. The end result will be a strong collaborative multi-national team of investigators with demonstrable capacity to address critical issues in head and neck oncology.